Publications
339 results found
Limbrey R, Howard L, 2015, Developments in the management and treatment of pulmonary embolism., European Respiratory Review, Vol: 24, Pages: 484-497, ISSN: 1600-0617
Pulmonary embolism (PE) is a serious and costly disease for patients and healthcare systems. Guidelines emphasise the importance of differentiating between patients who are at high risk of mortality (those with shock and/or hypotension), who may be candidates for thrombolytic therapy or surgery, and those with less severe presentations. Recent clinical studies and guidelines have focused particularly on risk stratification of intermediate-risk patients. Although the use of thrombolysis has been investigated in these patients, anticoagulation remains the standard treatment approach. Individual risk stratification directs initial treatment. Rates of recurrence differ between subgroups of patients with PE; therefore, a review of provoking factors, along with the risks of morbidity and bleeding, guides the duration of ongoing anticoagulation. The direct oral anticoagulants have shown similar efficacy and, in some cases, reduced major bleeding compared with standard approaches for acute treatment. They also offer the potential to reduce the burden on patients and outpatient services in the post-hospital phase. Rivaroxaban, dabigatran and apixaban have been shown to reduce the risk of recurrent venous thromboembolism versus placebo, when given for >12 months. Patients receiving direct oral anticoagulants do not require regular coagulation monitoring, but follow-up, ideally in a specialist PE clinic in consultation with primary care providers, is recommended.
Kechyn S, Barnes G, Thongmee A, et al., 2015, Effect of apelin on cardiopulmonary performance during endurance exercise, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Brash L, Barnes G, Brewis M, et al., 2015, Apelin improves cardiac output in patients with pulmonary arterial hypertension, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 8
Su J, Manisty C, Parker K, et al., 2015, Right Ventriculo-Arterial Interaction in Health and Disease as Assessed by Wave Intensity Analysis, ACTA PHYSIOLOGICA, Vol: 215, Pages: 71-71, ISSN: 1748-1708
Su J, Charalampopoulos A, Simonsen U, et al., 2015, Impact of atrial contraction on diagnosis of pre- versus post-capillary pulmonary hypertension, Congress of the European-Society-of-Cardiology (ESC), Publisher: Oxford University Press (OUP), Pages: 1039-1040, ISSN: 1522-9645
Gin-Sing W, Gibbs S, Howard L, et al., 2015, Audit of prostanoid use in a nationally designated PH centre, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 454-455, ISSN: 0195-668X
Dawes T, De Marvao A, Shi W, et al., 2015, Prognostic value of right heart adaptation to pulmonary arterial hypertension: a prospective cohort study, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 708-709, ISSN: 0195-668X
Rehman MB, Howard LS, Gibbs JSR, et al., 2015, Right ventricular function assessed by 2D speckle-tracking echocardiography in pulmonary hypertension. Relation with cardio-pulmonary exercise testing, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 964-964, ISSN: 0195-668X
Ruiter G, Manders E, Happé CM, et al., 2015, Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency., Pulmonary Circulation, Vol: 5, Pages: 466-472, ISSN: 2045-8940
In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal [Formula: see text] were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. ( TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01288651).
Schreiber K, Sciascia S, Breen K, et al., 2015, Proposed trial: hypatia - a prospective randomised controlled trial of hydroxychoroquine versus placebo during pregnancy in women with antiphospholipid antibodies, XXV Congress of the International Society on Thrombosis and Haemostasis, Publisher: Wiley, Pages: 281-281, ISSN: 1538-7836
Becattini C, At C, Agnelli G, et al., 2015, Risk stratification of patients with acute symptomatic pulmonary embolism based on presence or absence of deep vein thrombosis: systematic review and metaanalysis, ISTH 2015 Congress, Publisher: Wiley, Pages: 122-122, ISSN: 1538-7933
Low AT, Howard L, Harrison C, et al., 2015, Pulmonary arterial hypertension exacerbated by ruxolitinib, Haematologica, Vol: 100, Pages: E244-E245, ISSN: 0390-6078
Thom HHZ, Capkun G, Cerulli A, et al., 2015, Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension, BMC Medical Research Methodology, Vol: 15, ISSN: 1471-2288
Background: Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening directcomparisons of two or more treatments for the management of disease by combining evidence from multiplestudies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted torandomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to includesingle-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate themethod with an indirect comparison of treatments for pulmonary arterial hypertension (PAH).Methods: Our method uses a random effects model for placebo improvements to include single-arm observationalstudies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjustedcontinuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-armRCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAHcombining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs andsingle-arm observational studies, both identified by a systematic review.Results: Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-ontherapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCTevidence available. However, the credible intervals of our posterior estimates were wide so the overall results wereinconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice.Conclusions: Our method for the inclusion of single-arm observational studies allows the performance of indirectcomparisons that had previously not been possible due to incomplete networks composed solely of available RCTs.We also built on many recent innovations to enable researchers to use both aggregate data
George PM, Fagerbrink S, Meehan S, et al., 2015, Effects Of Pulmonary Embolism On Medium Term Cardiopulmonary Physiology: A Prospective Cohort Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Howard LS, Ferrari P, Mehta S, 2014, Physicians' and patients' expectations of therapies for pulmonary arterial hypertension: where do they meet?, Eur Respir Rev, Vol: 23, Pages: 458-468
In recent years, many new, effective therapies for pulmonary arterial hypertension (PAH) have become available and are widely used, yet the long-term prognosis for patients with PAH remains poor. In the absence of a cure, physicians' expectations of PAH-specific therapies are to: 1) improve patients' symptoms and functional capacity; 2) slow disease progression; and 3) improve survival. However, patients with PAH may prioritise other more tangible needs, such as improvements in their ability to carry out their daily tasks and increase their quality of life. Patients with PAH have also called out for social and emotional support from their physicians, caregivers, families and patient associations. Therefore, it is necessary that clinical trials of PAH-specific treatments include end-points that are meaningful to both patients and physicians, and that a multidisciplinary approach to the management of patients with PAH takes into consideration the broader aspects of patients' and caregivers' needs and wishes beyond simple physiological measurements.
Charalampopoulos A, Howard LS, Tzoulaki I, et al., 2014, Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors, PULMONARY CIRCULATION, Vol: 4, Pages: 669-678, ISSN: 2045-8932
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- Citations: 17
Howard LSGE, Santhirapala V, Murphy K, et al., 2014, Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations, CHEST, Vol: 146, Pages: 709-718, ISSN: 0012-3692
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- Citations: 18
Corte TJ, Keir GJ, Dimopoulos K, et al., 2014, Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 208-217, ISSN: 1073-449X
Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality.Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group.Methods: In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks.Measurements and Main Results: Sixty patients (42 men; mean age, 66.6 ± 9.2 yr), with a mean pulmonary artery pressure of 36.0 (± 8.9) mm Hg, PVRi 13.0 (± 6.7) Wood Units/m2 and reduced cardiac index of 2.21 (± 0.5) L/min/m2 were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change in functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group).Conclusions: This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP.
Wojciak-Stothard B, Abdul-Salam VB, Lao KH, et al., 2014, Aberrant chloride intracellular channel 4 expression contributes to endothelial dysfunction in pulmonary arterial hypertension, Circulation, Vol: 129, Pages: 1770-1780, ISSN: 0009-7322
Background—Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension.Methods and Results—CLIC4 protein expression was increased in plasma and blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension and in the pulmonary vascular endothelium of 3 rat models of pulmonary hypertension. CLIC4 gene deletion markedly attenuated the development of chronic hypoxia-induced pulmonary hypertension in mice. Adenoviral overexpression of CLIC4 in cultured human pulmonary artery endothelial cells compromised pulmonary endothelial barrier function and enhanced their survival and angiogenic capacity, whereas CLIC4 shRNA had an inhibitory effect. Similarly, inhibition of CLIC4 expression in blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension attenuated the abnormal angiogenic behavior that characterizes these cells. The mechanism of CLIC4 effects involves p65-mediated activation of nuclear factor-κB, followed by stabilization of hypoxia-inducible factor-1α and increased downstream production of vascular endothelial growth factor and endothelin-1.Conclusion—Increased CLIC4 expression is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension.
Ruiter G, Lanser IJ, de Man FS, et al., 2014, Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension, RHEUMATOLOGY, Vol: 53, Pages: 285-292, ISSN: 1462-0324
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- Citations: 49
Howard LS, 2014, Thrombolytic therapy for submassive pulmonary embolus? PRO viewpoint, THORAX, Vol: 69, Pages: 103-+, ISSN: 0040-6376
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- Citations: 2
Ruiter G, Manders E, Happe C, et al., 2014, Treatment Of Iron Deficiency In Pulmonary Hypertension, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X
McLaughlin VV, Gaine SP, Howard LS, et al., 2013, Treatment Goals of Pulmonary Hypertension, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 62, Pages: D73-D81, ISSN: 0735-1097
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- Citations: 214
Mukherjee B, Chan E, Murphy K, et al., 2013, THE DIAGNOSTIC VALUE OF MEASURING AAG DURING EXERCISE IN PATIENTS WITH PULMONARY HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A27-A27, ISSN: 0040-6376
Santhirapala V, Howard LSG, Murphy K, et al., 2013, DYSPNEA AND EXERCISE CAPACITY ARE NOT RELATED TO ARTERIAL HYPOXEMIA IN THE ABSENCE OF ALVEOLAR HYPOXIA: PROSPECTIVE STUDIES IN PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A24-A24, ISSN: 0040-6376
Guillevin L, Armstrong I, Aldrighetti R, et al., 2013, Understanding the impact of pulmonary arterial hypertension on patients' and carers' lives., Eur Respir Rev, Vol: 22, Pages: 535-542
Pulmonary arterial hypertension (PAH) is a rare, debilitating and rapidly progressive disease. Although there have been important medical advances in PAH management, the search for a cure continues. Despite an increased understanding of the disease, data on the wider effect of PAH on patients and carers, beyond the clinical symptoms, are still limited. In order to explore this, a large-scale international survey investigated four key areas affected by PAH (physical and practical, emotional, social, and information needs) and provides new insight into patients' and carers' experiences of living with the disease. The results from the survey highlight not only the limited ability of patients to carry out everyday tasks, but also the financial impact and social isolation experienced by both patients and carers. The study confirmed that a decline in a patient's World Health Organization functional class, which indicates an increase in clinical severity of the disease, is associated with greater limitations. Results from the survey demonstrate the need for multidisciplinary PAH management and a comprehensive standard of care to assess and improve all aspects of well-being for both patients and carers. In addition, they underline the need for updated PAH guidelines that address these needs.
Howard LS, 2013, Last call for the flight simulation test?, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, Pages: 1175-1177, ISSN: 0903-1936
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- Citations: 10
Keir G, Corte T, Parfitt L, et al., 2013, Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia: A randomized, double-blind, placebo-controlled study, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
Ferrari P, Armstrong I, Aldrighetti R, et al., 2013, Impact of pulmonary arterial hypertension (PAH) on the lives of patients and carers, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
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- Citations: 2
Ling Y, Johnson M, Kiely D, et al., 2013, Prognostic predictors in younger and older incident idiopathic pulmonary arterial hypertension, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
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